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Am J Physiol Heart Circ Physiol. 2011 Nov;301(5):H1952-64. doi: 10.1152/ajpheart.00635.2011. Epub 2011 Sep 9.

GATA6 reporter gene reveals myocardial phenotypic heterogeneity that is related to variations in gap junction coupling.

Author information

1
New York Medical College/Westchester Medical Center Stem Cell Laboratory, Department of Physiology, New York Medical College, Valhalla, NY, USA.

Abstract

This study examined transgenic mice whose expression of a β-galactosidase (lacZ) reporter is driven by a GATA6 gene enhancer. Previous investigations established that transcription of the transgene was associated with precardiac mesoderm and primary heart tube myocardium, which decreased progressively, so that its expression was no longer observed within ventricular myocardium by midgestation. Expression of this reporter in the adult was investigated for insights into myocyte homeostasis and cardiovascular biology. Morphometric analysis determined that <1% of myocytes, often found in small clusters, express this GATA6-associated reporter in the adult heart. LacZ expression was also found in the ascending aorta. Myocardial expression of the transgene was not associated with a proliferative phenotype or new myocyte formation, as lacZ-positive myocytes neither labeled with cell division markers nor following 5-bromodeoxyuridine pulse-chase experimentation. Despite exhibiting normal adherens junctions, these myocytes appeared to exhibit decreased connexin 43 gap junctions. Treatment with the gap junctional blocker heptanol both in vivo and in culture elevated myocardial β-galactosidase activity, suggesting that deficient gap junctional communication underlies expression of the transgenic reporter. LacZ expression within the myocardium was also enhanced in response to cryoinjury and isoproterenol-induced hypertrophy. These results reveal a previously uncharacterized phenotypic heterogeneity in the myocardium and suggest that decreased gap junctional coupling leads to induction of a signaling pathway that utilizes a unique GATA6 enhancer. Upregulation of lacZ reporter gene expression following cardiac injury indicates this transgenic mouse may serve as a model for examining the transition of the heart from healthy to pathological states.

PMID:
21908788
PMCID:
PMC3213955
DOI:
10.1152/ajpheart.00635.2011
[Indexed for MEDLINE]
Free PMC Article

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